Subthalamic Nucleus Stimulation Tames Severe OCD

Action Points

Point out to interested patients that in this preliminary study a surgical intervention lessened the severity of severe refractory obsessive-compulsive disorder but also carried a substantial risk of serious adverse events.

PARIS, Nov. 20 -- Patients with severe, refractory obsessive-compulsive disorder (OCD) found some relief of symptoms after stimulation of the brain's subthalamic nucleus, a small preliminary study showed.

The current treatment for OCD -- one of the most disabling of the chronic psychiatric disorders -- consists of a combination of serotonin-reuptake inhibitors and cognitive-behavioral therapy, the researchers, members of the French Obsessive Compulsive Stimulation study group, wrote.

With this treatment, however, 25% to 40% of patients have persistent symptoms and lasting functional repercussions, they said.

Studies of stimulation in patients with Parkinson's disease and other movement disorders have highlighted the putative role of the subthalamic nucleus in behavioral integration and the efficacy of stimulation in reducing repetitive behaviors, anxiety, obsessive-compulsive symptoms, and OCD, they said.

These results and the ability to target small, well-defined structures suggested the subthalamic nucleus as a target for treating highly resistant OCD, Dr. Mallet's team wrote.

In their study, conducted at 10 academic centers in France, the subthalamic nucleus was preoperatively targeted with stereotactic MRI and, depending on the local surgical protocol, by ventriculography, with additional targeting performed by the coordinating center.

The target for electrode placement in the 16 patients enrolled was 2 mm anterior to and 1 mm medial to the target that is used in patients with Parkinson's disease, at the boundary of the associative and limbic territories of the subthalamic nucleus.

In the 10-month, crossover, double-blind study, assessing the efficacy and safety of stimulation of the subthalamic nucleus, eight patients were assigned to undergo active stimulation followed by sham stimulation, and eight underwent sham stimulation followed by active stimulation.

The study was designed with two three-month phases, separated by a one-month washout period.

Patients were 18 to 20 years old with a primary diagnosis of OCD, disease duration of more than five years, a score of more than 25 (0 to 40) on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), and no response to drug therapy.

The primary outcome measure was the severity of OCD, as assessed by the Yale-Brown scale at the end of the two three-month periods.

General psychopathologic findings, functioning, and tolerance were assessed with standardized psychiatric scales, the Global Assessment of Functioning (GAF) scale, and neuropsychological tests.

After active stimulation of the subthalamic nucleus, the Yale-Brown score was significantly lower than the score after sham stimulation (mean 19Â±8 versus 28Â±7; P=0.01).

No significant carry-over effect in Yale-Brown (P=0.71) was detected, indicating that the effects of the first treatment period did not persist after the washout period.

The ratings of neuropsychological measures, depression, and anxiety were not modified by stimulation.

There were 15 serious adverse events overall, of which four were related to surgery.

The most serious event included one intracerebral hemorrhage leading to a permanent finger palsy and two infections requiring removal of the pulse generator. There was also a transient case of diplopia with perielectrode edema.

Other serious events occurred in the first month of stimulation and were transient.

Therefore, the researchers said, the benefits of this surgical treatment should be weighed against the potential occurrence of serious events.

In this study, hypomania was the main serious psychiatric adverse event. The fact that it resolved after adjustment of the stimulation settings highlights the need for multidisciplinary expertise in the medical care of patients being treated in this manner, they advised.

In addition to its small size and short duration, the multicenter design of this study had other potential design limitations, although variation in the targeting of the stimulation was minimized by anatomical and electrophysical identification performed simultaneously by local and coordinating teams.

Patients with unexpected responses were examined thoroughly at the detailed clinical follow-up examination required by the study protocol, the researchers wrote.

Moreover, adjustment of the settings was intentionally limited to be under the threshold for the induction of side effects to help preserve the blinded nature of the protocol.

Thus, they said, continued follow-up of patients undergoing subthalamic nucleus stimulation is needed to assess any long-term effects that have not yet been identified.

The occurrence of severe adverse events and the study limitations highlight the need for larger studies with longer follow-up.

In addition, the researchers said, a comparison with other stimulation targets and surgical procedures would be desirable, as would an evaluation of the long-term benefits of the surgical treatment, notably with respect to patients' quality of life and their ability to function in social and work environments.

This study was supported by grants from the Programme Hospitalier de la Recherche Clinique Assistance Publique-HÃ´pitaux de Paris and the Agence Nationale de la Recherche Program for Young Researchers. The stimulators were purchased from Medtronic, which had no role in the study. Medtronic provided funds for the study investigators' meetings during the study.

Dr. Millet reported grant support from Medtronic. No other potential conflict of interest relevant to this article was reported.

Reviewed by Zalman S. Agus, MD Emeritus Professor University of Pennsylvania School of Medicine

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